Quantifying the need for enhanced case management for TB patients as part of TB cohort audit in the North West of England: a descriptive study.

BACKGROUND: Patients with TB have diverse and often challenging clinical and social needs that may hamper successful treatment outcomes. Understanding the need for additional support during treatment (enhanced case management, or ECM) is important for workforce capacity planning. North West England TB Cohort Audit (TBCA) has introduced a 4-level ECM classification system (ECM 0-3) to quantify the need for ECM in the region. This study describes the data from the first 2 years of ECM classification. METHODS: Data collected between April 2013 and July 2015 were used to analyse the proportions of patients allocated to each ECM level and the prevalence of social and clinical factors indicating need for ECM. Single variable and multivariable logistic regression models were constructed to examine the association between ECM level and treatment outcome. RESULTS: Of 1714 notified cases 99.8% were assigned an ECM level: 31% ECM1, 19% ECM2 and 14% ECM3. The most common factors indicating need for ECM were language barriers (20.3%) and clinical complexity (16.9%). 1342/1493 (89.9%) of drug-sensitive, non-CNS cases completed treatment within 12 months. Patients in ECM2 and 3 were less likely to complete treatment at 12 months than patients in ECM0 (adjusted OR 0.47 [95% CI 0.27-0.84] and 0.23 [0.13-0.41] respectively). CONCLUSIONS: Use of TBCA to quantify different levels of need for ECM is feasible and has demonstrated that social and clinical complexity is common in the region. Results will inform regional workforce planning and assist development of innovative methods to improve treatment outcomes in these vulnerable groups.

Association between sputum smear status and local immune responses at the site of disease in HIV-infected patients with pulmonary tuberculosis.

Infection with human immunodeficiency virus (HIV) may affect the clinical presentation of pulmonary tuberculosis (TB). To investigate the association between sputum smear status at presentation and local pulmonary immune responses in HIV-infected patients with pulmonary TB, we compared the cellular and cytokine profiles in bronchoalveolar lavage (BAL) fluid obtained from the site of lung disease in 22 sputum smear- and culture-positive, and 17 sputum smear-negative but culture-positive pulmonary TB patients. Smear-positive patients had significantly higher BAL fluid concentrations of IL-6 (p=0.007), IL-8 (p=0.02), IL-10 (p=0.03) and IFN-gamma (p=0.008) than smear-negative patients. No significant differences in the proportions of examined BAL cells were found. We concluded that sputum smear-positive TB was associated with greater pro-inflammatory and immunomodulatory cytokine responses at the site of lung disease than sputum smear-negative disease. The local immune responses may affect the clinical presentation of active pulmonary TB in HIV-infected patients.

"He will ask why the child gets sick so often": the gendered dynamics of intra-household bargaining over healthcare for children with fever in the Volta Region of Ghana.

This paper explores the gendered dynamics of intra-household bargaining around treatment seeking for children with fever revealed through two qualitative research studies in the Volta Region of Ghana, and discusses the influence of different gender and health discourses on the likely policy implications drawn from such findings. Methods used included focus group discussions, in-depth and critical incidence interviews, and Participatory Learning and Action methods. We found that treatment seeking behaviour for children was influenced by norms of decision-making power and 'ownership' of children, access to and control over resources to pay for treatment, norms of responsibility for payment, marital status, household living arrangements, and the quality of relationships between mothers, fathers and elders. However, the implications of these findings may be interpreted from different perspectives. Most studies that have considered gender in relation to malaria have done so within a narrow biomedical approach to health that focuses only on the outcomes of gender relations in terms of the (non-)utilisation of allopathic healthcare. However, we argue that a 'gender transformatory' approach, which aims to promote women's empowerment, needs to include but go beyond this model, to consider broader potential outcomes of intra-household bargaining for women's and men's interests, including their livelihoods and 'bargaining positions'.

Differential drug susceptibility of intracellular and extracellular tuberculosis, and the impact of P-glycoprotein.

If tuberculosis therapy is to be shortened it is imperative that the sterilising activity of current and future anti-tuberculosis drugs is enhanced. Intracellular Mycobacterium tuberculosis (MTB) phagocytosed by macrophages may be a key subpopulation of bacteria that are less readily eliminated by therapy. Here we investigate whether macrophages provide MTB with a pharmacological sanctuary site, making them less susceptible to chemotherapy than extracellular bacilli. Intracellular drug activity was determined by a novel colorimetric method that measures the ability of a drug to protect A-THP1 cells from infection-mediated cell death by H37Rv. Extracellular bactericidal activity was determined by the microplate alamar blue assay (MABA). Further, the effect of P-glycoprotein (P-gp) expressed on macrophages on the intracellular kill of H37Rv was assessed. To screen the anti-tuberculosis drugs for P-gp substrate specificity, their toxicity and cellular accumulation were determined in CEM and CEM(VBL100) cells. Intracellular and extracellular anti-tuberculosis drug activity following 7-day treatment with isoniazid (mean EC(50)+/-SD: 36.7+/-2.2 and 57.2+/-2.5 ng/mL, respectively) and ethambutol (243+/-95 and 263+/-12 ng/mL, respectively) were similar. However, for rifampicin a higher concentration was required to kill intracellular (148+/-32 ng/mL) versus extracellular (1.27+/-0.02 ng/mL) bacilli. The P-gp inhibitor tariquidar, significantly increased intracellular kill of H37Rv by ethambutol and rifampicin and both of these drugs were shown to be substrates for P-gp using the P-gp overexpressing CEM(VBL100) cells. We observed a large discrepancy between intracellular and extracellular activity of rifampicin (but not with isoniazid or ethambutol). Several factors could have accounted for this including inoculum size, media and cell-mediated metabolism. These factors make the comparison of intracellular and extracellular drug activity complex. However, the intracellular assay described here has potential for studying the impact of host proteins (such as drug transporters) on the intracellular activity of drugs, and has been used successfully here to demonstrate that both rifampicin and ethambutol are substrates for P-gp.

Assessing new strategies for TB diagnosis in low- and middle-income countries.

In this manuscript, we report the current situation of tuberculosis globally and in Brazil, the need for new strategies toward tuberculosis control, focusing on new diagnostic technologies. Critical comments are given on the state of the art regarding the evaluation of new health technologies, degree of scientific evidence needed, evaluation of clinical impact, cost-effectiveness of incorporation into the health system and the social impact.

Rural poverty and delayed presentation to tuberculosis services in Ethiopia.

To measure time to initial presentation and assess factors influencing the decision to seek medical attention, we interviewed 243 patients undergoing sputum examination for the diagnosis of tuberculosis (TB) at a rural health centre near Awassa, Ethiopia. A structured questionnaire was used. Median (mean+SD) patient delay was 4.3 (9.8+12.4) weeks. Delays over 4 weeks were significantly associated with rural residence, transport time over 2 h, overnight travel, transport cost exceeding US $1.40, having sold personal assets prior to the visit, and use of traditional medicine. The majority of patients cited economic or logistical barriers to health care when asked directly about causes of delay. Case-finding strategies for TB must be sensitive to patient delay and health systems must become more accessible in rural areas.

Short communication: colour vision and proficiency in diagnostic microscopy.

The microscopical diagnosis of infectious diseases is an essential medical laboratory service in resource-poor countries. We conducted an external quality assessment (EQA) of peripheral laboratories in southern Ethiopia using a panel of 20 ready-prepared sputum and blood smears containing either no pathogens or locally common pathogens. Microscopists also undertook a colour discrimination test (Farnsworth-Munsell 100 hue test). Twenty microscopists from 10 health centres participated. Their microscopy results were compared with that of the EQA controllers. Their Kappa indices of agreement ranged from 0.1 to 0.89 (mean+/-SD: 0.58+/-0.21). Kappa values were analysed according to microscopists' colour discrimination ability. The Kappa indices for the correct reading of diagnostic smears were associated with the colour vision ability of the technicians. Our results suggest that routine quality improvement activities may not achieve their desired effect if the colour discrimination abilities of technicians are not considered.